RESUMO
AIM: To better understand the aetiologies of epileptic spasms in infants, as well as the safety and efficacy of high dose corticosteroids in tuberculosis and human immunodeficiency virus (HIV) endemic resource-limited settings. METHOD: This was a retrospective analysis of infants with epileptic spasms managed at the tertiary referral centres in the Western Cape, South Africa. RESULTS: Of 175 children with epileptic spasms, the median age at onset was 6 months (interquartile range 4-8 months). Structural aetiologies were most common (115 out of 175 [66%]), with two-thirds related to perinatal insults. A lead time to treatment (LTTT) of less than 1 month was more likely in the epileptic encephalopathy/developmental and epileptic encephalopathy (DEE) group: 58 out of 92 (63%), compared to 28 out of 76 (37%) of those with developmental encephalopathy (p = 0.001). Failure to recognize preceding developmental delay was common. Ninety-nine children (57%) received first line hormonal therapy such as adrenocorticotropic hormone. A total of 111 out of 172 children (65%) from the developmental encephalopathy and epileptic encephalopathy/DEE groups had clinical and/or electroencephalogram resolution of spasms within 14 days. In our population, children in whom an aetiology could not be identified were statistically more likely to have moderate to profound developmental delay at 1 year of age: 33 out of 44 (p = 0.001). Based on reported incidence of epileptic spasms, 23 to 58 cases per annum would be expected but a far smaller proportion presented to our centres. INTERPRETATION: Whilst this is the largest cohort of infants with epileptic spasms from sub-Saharan Africa, the study size is less than expected; this may reflect misdiagnosis and failure of referral pathways. Despite a reported shorter LTTT, infants with DEE had worse developmental outcomes compared to international studies. Hormonal therapy was safe and effective in our setting, despite exposure to high levels of tuberculosis and HIV. WHAT THIS PAPER ADDS: The number of unreferred cases of epileptic spasms in South Africa remains high. Caregivers and health care workers in primary care facilities often fail to recognize developmental delay. The burden of disease from hypoxic-ischaemic encephalopathy remains high in our resource-limited setting. Hormonal treatment (e.g. adrenocorticotropic hormone) was safe and effective despite the high prevalence of human immunodeficiency virus and tuberculosis.
Assuntos
Infecções por HIV , Espasmos Infantis , Lactente , Criança , Humanos , Adulto , África do Sul , Estudos Retrospectivos , Espasmos Infantis/tratamento farmacológico , Hormônio Adrenocorticotrópico/uso terapêutico , Espasmo/complicações , Espasmo/tratamento farmacológico , Eletroencefalografia/efeitos adversos , Infecções por HIV/complicaçõesRESUMO
BACKGROUND: Acute kidney injury (AKI) is the most common complication of perinatal asphyxia. Recent research indicates that urine neutrophil gelatinase-associated lipocalin (NGAL) is an early marker for AKI; yet, there is a paucity of data about its use in term neonates with perinatal asphyxia. METHODS: A prospective cohort study was conducted on 108 term babies in the new-born unit of Pumwani Maternity Hospital and Kenyatta National Hospital. Urine NGAL and serum creatinine were measured in 108 term asphyxiated neonates on days 1 and 3 of life. RESULTS: One-hundred and eight patients were recruited (male:female 1.4:1). At a cut-off of 250 ng/ml, urine NGAL had an acceptable discriminative capability of predicting AKI (area under the curve 0.724). The sensitivity, specificity, positive and negative predictive value and likelihood ratios were 88, 56, 30, 95%, 2 and 0.2 respectively. Urine NGAL levels were significantly higher in patients with AKI compared with those without AKI. An NGAL level greater than 250 ng/ml on day 1 was significantly associated with severe hypoxic ischaemic encephalopathy (HIE); odds ratio = 8.9 (95% CI 1.78-37.69) and mortality; odds ratio = 8.9 (95% CI 1.78-37.69). CONCLUSION: Urine NGAL is a good screening test for the early diagnosis of AKI. It is also a predictor of mortality and severity of HIE in asphyxiated neonates.
Assuntos
Proteínas de Fase Aguda/urina , Asfixia Neonatal/urina , Lipocalinas/urina , Proteínas Proto-Oncogênicas/urina , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Asfixia Neonatal/complicações , Asfixia Neonatal/mortalidade , Peso ao Nascer , Encefalopatias Metabólicas/etiologia , Estudos de Coortes , Comorbidade , Creatinina/sangue , Feminino , Humanos , Lactente , Lipocalina-2 , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de SobrevidaRESUMO
OBJECTIVES: The developmental and epileptic encephalopathies (DEE) are a heterogeneous group of rare neurodevelopmental disorders, characterised by early-onset seizures that are often intractable, electroencephalographic abnormalities, and developmental delay or regression. There is a paucity of data from sub-Saharan Africa on the genetic basis of DEE. The aim of this study was to investigate the genetic background of DEE using targeted next generation sequencing (NGS) analysis in a tertiary pediatric neurology outpatient department at Tygerberg Hospital, South Africa. In addition, we assessed the value of the genetic results to the parents and managing physicians. METHODS: A prospective cohort study of 41 consecutive children with DEE (onset before 3 years of age) that were recruited over a 2-year period (2019-2021). Pre- and post-test genetic counselling were offered to all study participants. The results were categorized as either: positive (pathogenic/likely pathogenic variant identified), inconclusive (variant(s) of unknown significance identified), or negative (no variants identified). Result interpretation and careful matching of the variant to the clinical phenotype was performed. Subsequently, questionnaires were administered to both the physicians and the parents. RESULTS: A genetic underlying cause for DEE was identified in 18 of 41 children (diagnostic yield 43.9%). Variants in SCN1A (n=7), KANSL1 (n=2), KCNQ2 (n=2) and CDKL5 (n=2) were identified in more than one patient. Rarer genes included IQSEC2, SMC1A and STXBP1. All of the identified pathogenic variants fully explained and matched the respective phenotypic description of the patient at the time of clinical diagnosis. In 26% of patients the genetic result facilitated precision medicine management changes to anti-seizure medication. Both parents and physicians expressed benefit of genetic testing in patients with DEE. CONCLUSION: Targeted NGS analysis proved an efficient diagnostic tool in detection of a genetic cause of DEE in a large proportion of South African children. The 43.9% diagnostic yield is similar to previously reported international pediatric cohorts. Additionally, the genetic findings proved useful for targeted therapeutic decision-making and accurate genetic counseling.
Assuntos
Espasmos Infantis , Testes Genéticos/métodos , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Estudos Prospectivos , África do Sul , Espasmos Infantis/diagnóstico , Espasmos Infantis/genética , Centros de Atenção TerciáriaRESUMO
Syringomyelia associated with tuberculous meningitis (TBM) is an extremely rare condition. Only a few adult cases have been reported. A 12-year-old woman, who previously suffered TBM at the age of 6 months, presented with a long-standing history of right upper limb panhypertrophy, dissociate anaesthesia, frequent headaches, scoliosis and acquired macrocephaly. MRI demonstrated hydrocephalus, descent of the cerebral tonsils and an intramedullary syrinx extending from C2 to L1. Endoscopic third ventriculostomy (ETV) leads to reduction in the size of the syringomyelia and resolution of the thermoanaesthesia. This case highlights a very rare long-term complication associated with childhood TBM and the potential benefit offered by ETV.
Assuntos
Malformação de Arnold-Chiari , Siringomielia , Terceiro Ventrículo , Tuberculose Meníngea , Adulto , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/cirurgia , Criança , Feminino , Humanos , Hipertrofia , Lactente , Imageamento por Ressonância Magnética , Siringomielia/diagnóstico por imagem , Siringomielia/etiologia , Siringomielia/cirurgia , Tuberculose Meníngea/complicações , Extremidade SuperiorRESUMO
We report on a unique case of a 7-year-old girl with new onset ocular myasthenia gravis shortly after recovery from multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2 infection. The diagnosis of myasthenia gravis was based on suggestive symptoms of fatigable bilateral orbital ptosis, diplopia, positive ocular cold compression test and serum acetylcholine receptor antibody positivity, as well as a favourable treatment response to pyridostigmine. The addition of corticosteroids and methotrexate resulted in complete resolution of the ocular signs.
Assuntos
COVID-19 , Miastenia Gravis , Criança , Feminino , Humanos , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Receptores Colinérgicos , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
We herein report a case of a child with tuberculous meningitis and COVID-19 coinfection complicated by hydrocephalus, arterial ischaemic stroke and extensive cerebral sinus venous thrombosis. Both conditions induce a proinflammatory cytokine drive resulting, among others, in a prothrombotic state. The disruption of the coagulation system in this case was supported by elevated D-dimers, fibrinogen and ferritin levels, consistent with thrombotic complications reported in some adult patients infected with COVID-19. The child also exhibited prolonged viral shedding that suggests severe disease.